NCATS has developed novel allosteric inhibitors of cAbl that are able to cross the blood-brain barrier. A number of these allosteric inhibitors of wild type cAbl kinase that NCATS developed were found to have good CNS penetration and good pharmacokinetic properties. These compounds were sent to Dr. Klonish for evaluation against several glioblastoma cell lines. Additional testing of the compounds against all NCATS analogues will be carried out at NCATS with two glioblastoma cell lines. Currently, the assay is being adapted and optimizaed for high-throughput screening. In parallel, one of the most promising molecules has been scaled up for use in efficacy studies in glioma xenograft models.